OP0166 LONG-TERM FOLLOW-UP OF PATIENTS ADMINISTERED EMAPALUMAB, AN ANTI–INTERFERON-Γ MONOCLONAL ANTIBODY, TO TREAT MACROPHAGE ACTIVATION SYNDROME (MAS) SECONDARY TO SYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS (SJIA)
Authors: F. De Benedetti, A. Grom, P. Brogan, C. Bracaglia, M. Pardeo, G. Marucci, D. Eleftheriou, C. Papadopoulou, G. Schulert, P. Quartier, J. Antón, C. Laveille, R. Frederiksen, V. Asnaghi, M. Ballabio, P. Jacqmin, C. De Min
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> MAS, a form of secondary hemophagocytic lymphohistiocytosis (sHLH), is a severe, life-threatening complication of rheumatic diseases that occurs most frequently in patients (pts) with sJIA and adult-onset Still’s disease (AOSD). MAS is characterized by hyperinflammation and overproduction of interferon γ (IFNγ). Treatment with emapalumab, an anti-IFNγ monoclonal antibody, rapidly neutralized IFNγ and controlled MAS secondary to sJIA in pts with an inadequate response to high-dose glucocorticoids (GCs) in a phase 2 study (parent study).<sup>[1]</sup> <h3>Objectives</h3> To report outcomes and safety among pts with MAS treated with emapalumab after 12 months of follow-up. <h3>Methods</h3> The parent study enrolled pts with sJIA or AOSD who failed high-dose GCs (≥2 mg/kg/day). Pts who received emapalumab in the parent study (6 mg/kg on day [D] 0, followed by 3 mg/kg every 3 days until D15 and twice weekly until D28) and completed short-term follow-up (≥4 weeks) after last drug administration were invited to participate in this long-term follow-up study. Pts were assessed at follow-up Week (W) 2, W3, D30, D100, Month (M) 6 and M12. Emapalumab was not administered during follow-up. Overall MAS activity was monitored using a visual analog scale, comprehensive clinical evaluation and observation of pts‘ overall status. Serum samples for pharmacokinetic and pharmacodynamic analysis were collected at each study visit while serum emapalumab remained detectable. Safety was monitored throughout. <h3>Results</h3> All 14 pts (sJIA onset at &lt;16 yrs, n=13; 1 had onset at age 16 yrs, 7 months) in the parent study participated in this long-term follow-up study. 6 pts had a history of 19 MAS episodes prior to the parent study. All prior episodes were treated with high-dose GCs; pts were also treated with anakinra (n=7) and/or cyclosporine A (n=8). 13/14 patients achieved MAS remission by W8, with rapid IFNγ neutralization during the parent study, as shown by decreased CXCL9 levels versus baseline. GCs were rapidly tapered in all pts. 13/14 pts did not present with another MAS episode; 1 MAS episode was reported 11 months after the pt stopped emapalumab (serum emapalumab was undetectable). The terminal elimination phase for emapalumab was slow and linear during follow-up (median t<sub>½</sub>, 24 days). CXCL9 and soluble interleukin-2 receptor levels remained close to, or within, the normal range. GC tapering continued during follow-up: at M12, 5 pts were off GCs and 6 pts were receiving &lt;0.3 mg/kg/day of prednisone. 4 sJIA flares (without MAS) occurred during follow-up. In total, 37 adverse events (AEs) were reported by 12 patients, including 3 serious AEs (SAEs), all unrelated to emapalumab: 1 MAS reactivation, 1 sJIA flare and 1 ankle edema. All SAEs resolved spontaneously or with standard treatment. 10 infectious AEs (9 of viral origin) were reported during follow-up; 4 occurred when serum emapalumab levels were measurable and 6 after emapalumab became undetectable (Table 1). No new safety signals were observed. All pts were alive at M12. <h3>Conclusion</h3> Most pts with MAS who had failed high-dose GCs and responded to emapalumab remained in remission and continued GC tapering during 12 months of follow-up. Any viral infections during follow-up resolved spontaneously or with standard treatment, confirming the favorable safety profile of emapalumab. A pivotal clinical trial of emapalumab in patients with sHLH and underlying rheumatic disease is ongoing (EMERALD; NCT05001737). <h3>Reference</h3> [1] De Benedetti F, et al. <i>Ann Rheum Dis</i> 2022;81(Suppl 1):128 (OP0193). <h3>Acknowledgements</h3> Medical writing assistance was provided by Blair Hesp PhD CMPP of Kainic Medical Communications Ltd. (Dunedin, New Zealand), which was funded by Sobi AG (Basel, Switzerland). <h3>Disclosure of Interests</h3> Fabrizio De Benedetti Consultant of: AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis, Novimmune, Grant/research support from: AbbVie, Sobi, Pfizer, Roche, Sanofi, Novartis, Novimmune, Alexei Grom Consultant of: Novartis, AB2 Bio, Novimmune, Sobi, Paul Brogan Consultant of: Sobi, Novartis, Roche, UCB, Claudia Bracaglia: None declared, Manuela Pardeo: None declared, Giulia Marucci: None declared, Despina Eleftheriou Speakers bureau: Sobi, Charalampia Papadopoulou Speakers bureau: Sobi, Grant Schulert Consultant of: Novartis, Sobi, Novimmune, AB2 Bio, Pierre Quartier Speakers bureau: AbbVie, Chugai-Roche, Lilly, Novartis, Pfizer, Sobi, Consultant of: AbbVie, Chugai-Roche, Lilly, Novartis, Pfizer, Sobi, Jordi Antón Consultant of: Sobi, Novartis, Roche, Pfizer, AbbVie, GSK, Christian Laveille Consultant of: Sobi, Rikke Frederiksen Employee of: Former employee of Sobi, Veronica Asnaghi Employee of: Former employee of Sobi, Maria Ballabio Employee of: Former employee of Sobi, Philippe Jacqmin Consultant of: Sobi, Cristina de Min Employee of: Former employee of Sobi.